Q09128 · CP24A_RAT
- Protein1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
- GeneCyp24a1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids514 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24-oxidation pathway, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D3) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D3) (PubMed:10231362, PubMed:16617161, PubMed:2026586).
With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid (PubMed:10231362, PubMed:16617161).
Hydroxylates at C-24 or C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol (PubMed:25727742).
Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:2026586).
With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid (PubMed:10231362, PubMed:16617161).
Hydroxylates at C-24 or C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol (PubMed:25727742).
Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:2026586).
Catalytic activity
- calcitriol + 2 H+ + O2 + 2 reduced [adrenodoxin] = calcitetrol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 2 H+ + O2 + 2 reduced [adrenodoxin] + secalciferol = 25-hydroxy-24-oxocalciol + 2 H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 25-hydroxy-24-oxocalciol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 23S,25-dihydroxy-24-oxocholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 20S,23-dihydroxycholecalciferol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 20S,23,25-trihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 20S,23-dihydroxycholecalciferol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 20S,23,24-trihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 20S-hydroxycholecalciferol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 20S,25-dihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 20S-hydroxycholecalciferol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 20S,24S-dihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 20S-hydroxycholecalciferol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 20S,24R-dihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2.8 μM | calcidiol | |||||
0.19 μM | calcitriol |
pH Dependence
Optimum pH is 7.7.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrion | |
Molecular Function | 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity | |
Molecular Function | 1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity | |
Molecular Function | 25-hydroxycholecalciferol-23-hydroxylase activity | |
Molecular Function | 25-hydroxycholecalciferol-24-hydroxylase activity | |
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Molecular Function | vitamin D 24-hydroxylase activity | |
Molecular Function | vitamin D 25-hydroxylase activity | |
Biological Process | cellular response to vitamin D | |
Biological Process | osteoblast differentiation | |
Biological Process | response to vitamin D | |
Biological Process | vitamin D catabolic process | |
Biological Process | vitamin D metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended name1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
- EC number
- Short names24-OHase; Vitamin D(3) 24-hydroxylase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ09128
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 416 | Increases the C23:C24 hydroxylation ratio from 0.01 to 0.12. | ||||
Sequence: T → F | ||||||
Mutagenesis | 416 | Increases the C23:C24 hydroxylation ratio from 0.01 to 0.19. | ||||
Sequence: T → I | ||||||
Mutagenesis | 416 | Increases the C23:C24 hydroxylation ratio from 0.01 to 0.08. | ||||
Sequence: T → M | ||||||
Mutagenesis | 416 | Increases the C23:C24 hydroxylation ratio from 0.01 to 0.16. | ||||
Sequence: T → V | ||||||
Mutagenesis | 500 | Increases the C23:C24 hydroxylation ratio from 0.01 to 0.15. | ||||
Sequence: I → A | ||||||
Mutagenesis | 500 | Increases the C23:C24 hydroxylation ratio from 0.01 to 0.16. | ||||
Sequence: I → T or L | ||||||
Mutagenesis | 500 | Increases the C23:C24 hydroxylation ratio from 0.01 to 0.13. | ||||
Sequence: I → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for transit peptide, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-35 | Mitochondrion | ||||
Sequence: MSCPIDKRRTLIAFLRRLRDLGQPPRSVTSKASAS | ||||||
Chain | PRO_0000003617 | 36-514 | 1,25-dihydroxyvitamin D3 24-hydroxylase, mitochondrial | |||
Sequence: RAPKEVPLCPLMTDGETRNVTSLPGPTNWPLLGSLLEIFWKGGLKKQHDTLAEYHKKYGQIFRMKLGSFDSVHLGSPSLLEALYRTESAHPQRLEIKPWKAYRDHRNEAYGLMILEGQEWQRVRSAFQKKLMKPVEIMKLDKKINEVLADFLERMDELCDERGRIPDLYSELNKWSFESICLVLYEKRFGLLQKETEEEALTFITAIKTMMSTFGKMMVTPVELHKRLNTKVWQAHTLAWDTIFKSVKPCIDNRLQRYSQQPGADFLCDIYQQDHLSKKELYAAVTELQLAAVETTANSLMWILYNLSRNPQAQRRLLQEVQSVLPDNQTPRAEDLRNMPYLKACLKESMRLTPSVPFTTRTLDKPTVLGEYALPKGTVLTLNTQVLGSSEDNFEDSHKFRPERWLQKEKKINPFAHLPFGIGKRMCIGRRLAELQLHLALCWIIQKYDIVATDNEPVEMLHLGILVPSRELPIAFRPR |
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length514
- Mass (Da)59,448
- Last updated1996-10-01 v1
- Checksum2E5CC1CCBA3C2B91
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6A8M6 | A0A8I6A8M6_RAT | Cyp24a1 | 495 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X59506 EMBL· GenBank· DDBJ | CAA42093.1 EMBL· GenBank· DDBJ | mRNA | ||
L04618 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04608 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04609 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04610 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04611 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04612 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04613 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04614 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04615 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04616 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L04617 EMBL· GenBank· DDBJ | AAA42340.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC100059 EMBL· GenBank· DDBJ | AAI00060.1 EMBL· GenBank· DDBJ | mRNA | ||
Z28351 EMBL· GenBank· DDBJ | CAA82206.1 EMBL· GenBank· DDBJ | Genomic DNA |